Sterically governed selectivity in palladium-assisted allylic alkylation

Article abstract of DOI:10.1021/om1007264

The selectivity in the Pd-assisted allylic alkylation has been investigated in a system with a ligand tethered to the allylic moiety. Isolation of (η³-allyl)Pd complexes and stoichiometric reaction with malonate nucleophiles allowed separation

Full text of DOI:10.1021/om1007264

230 Organometallics 2011, 30, 230–238
DOI: 10.1021/om1007264
Sterically Governed Selectivity in Palladium-Assisted Allylic Alkylation
Jonatan Kleimark,† Charlotte Johansson,† Susanne Olsson,† Mikael Hakansson,†
˚
‡
Sverker Hansson, Bjorn Akermark, and Per-Ola Norrby*
§
,†
˚
€
†
˚
€
Department of Chemistry, University of Gothenburg, Kemigarden 4, SE-412 96 Goteborg, Sweden,
‡Astrazeneca, SE-151 85 So€derta€lje, Sweden, and §Arrhenius Laboratory, Department of Organic Chemistry,
Stockholm University, SE-106 91 Stockholm, Sweden
Received July 26, 2010
The selectivity in the Pd-assisted allylic alkylation has been investigated in a system with a ligand
tethered to the allylic moiety. Isolation of (η3-allyl)Pd complexes and stoichiometric reaction with
malonate nucleophiles allowed separation of various factors influencing the regioselectivity in a system
that cannot undergo apparent rotation. Unexpectedly, trans effects were found to have only a minor
influence on the selectivity, whereas changing the tether length could shift the preference from favored
internal to dominant terminal attack. DFT-assisted analysis revealed that the dominant selectivity-
determining factors are the forced rotation of the allylic moiety and an important steric repulsion from a
syn-alkyl substituent.
Introduction
known to be sensitive to many factors, such as steric and
electronic influences from the substrate substituents,5 regio-
chemical memory of the position of the leaving group,6 the
preferred configuration7,8 and dynamic exchange in the (η3-
allyl)Pd intermediate,9 the nucleophile,10 and the nature of
the ligands.4,11,12 For example, it could be shown that syn-
substituted (η3-allyl)Pd complexes have a strong preference
for terminal attack, whereas the corresponding anti-substituted
complexes gave product mixtures with significant amounts of
internal attack.7,8 The latter has important implications for the
possibilities of inducing asymmetry, since internal attack pro-
duces a new stereocenter. Ligand-induced distortions of the
intermediate have also been shown to have a strong effect on
the regiochemical preference in the nucleophilic attack.13 How-
ever, despite numerous advances we are still far from a com-
plete understanding of the behavior of (η3-allyl)Pd complexes.
For selected substrates, we can achieve very high selectivities,
but a general control of the regiochemistry in Pd-assisted allylic
alkylation still eludes us.
Palladium-assisted allylation is a standard reaction in the
toolbox of organic chemistry. The reaction is usually stereo-
specific, can be run under mild conditions with a large range
of nucleophiles, and tolerates a wide range of functional
groups.1 When employing stabilized carbanion nucleophiles
such as malonates, the reaction is known as allylic alkylation,
or the Tsuji-Trost reaction.2 The asymmetric version of this
reaction is a popular method for creating new chiral centers
while at the same time extending the carbon framework.3
The mechanism of the title reaction involves initial oxidative
addition of a Pd0 complex to an allylic substrate (e.g.,
acetate) to form an intermediate (η3-allyl)Pd complex, which
is attacked by a nucleophile to produce the final product with
loss of Pd0, Scheme 1. Both steps most commonly proceed
with inversion, giving overall retention.
Asymmetric versions of the Tsuji-Trost reaction are
frequently applied to substrates that yield symmetrically
substituted (η3-allyl)Pd intermediates, such as cycloalkenyl
or 1,3-diphenylallyl complexes.3 In such cases, enantioselec-
tivity is determined by the regioselectivity of the nucleophilic
attack.4 In unsymmetric cases, like the monosubstituted (η3-
allyl)Pd complex depicted in Scheme 1, the regioselectivity is
ꢀ
(5) (a) Szabo, K. J. Chem. Soc. Rev. 2001, 30, 136–143. (b) Branchadell,
~
V.; Moreno-Manas, M.; Pajuelo, F.; Pleixats, R. Organometallics 1999, 18,
4934–4941.
(6) Lloyd-Jones, G. C.; Stephen, S. C. Chem. Eur. J. 1998, 4, 2539–
2549.
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M. E.; Vitagliano, A. Organometallics 1992, 11, 3954–3964.
(8) Fristrup, P.; Jensen, T.; Hoppe, J.; Norrby, P.-O. Chem. Eur. J.
2006, 12, 5352–5360.
(9) Hansson, S.; Norrby, P.-O.; Sjogren, M.; Akermark, B.; Cucciolito,
M. E.; Giordano, F.; Vitagliano, A. Organometallics 1993, 12, 4940–4948.
(10) Kazmaier, U.; Stolz, D.; Kraemer, K.; Zumpe, F. L. Chem. Eur.
J. 2008, 14, 1322–1329.
*To whom correspondence should be addressed. E-mail: pon@chem.
gu.se.
(1) (a) Hartwig, J. F. Organotransition Metal Chemistry-From Bond-
ing to Catalysis; University Science Books: Sausalito, CA, 2010. (b) Tsuji, J.
Palladium Reagents and Catalysts: Innovations in Organic Synthesis;
Wiley: Chichester, UK, 1997.
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(b) Tsuji, J. In Handbook of Organopalladium Chemistry for Organic
Synthesis, Vol. 2; Negishi, E.-i., Ed.; Wiley: New York, 2002.
(3) (a) Trost, B. M.; Lee, C. In Catalytic Asymmetric Synthesis, 2nd
ed.; Ojima, I., Ed.; Wiley-VCH: New York, 2000; pp 593-649. (b) Pfaltz, A.;
Lautens, M. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N.;
Pfaltz, A.; Yamamoto, H., Eds.; Springer: Heidelberg, 1999; pp 833-886.
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pubs.acs.org/Organometallics
Published on Web 12/23/2010
2010 American Chemical Society

Article
Organometallics, Vol. 30, No. 2, 2011 231
However, the results were hard to interpret. It was known that
the regioselectivity could be strongly influenced by the syn-anti
equilibrium in the (η3-allyl)Pd intermediate,7,8 but we could not
at that time elucidate the preferred structure of the tethered
intermediate. Yoshida and co-workers have investigated the
effect of a removable pyridine tether,21 but they did not perform
a detailed analysis of the reasons for the good regioselectivity.
Krafft and co-workers studied catalytic systems with a range of
tethered ligands, including alkenes22 and sulfides,23 but they did
not ascertain which ligands were bound to Pd during the
nucleophilic attack. Some of their results indicate that, in a
catalytic system, the tethered heteroatom interacts with the
approaching nucleophile, not Pd. For the purpose of investigat-
ing the trans effect from the ligands, we must ascertain the
coordination geometry, which is most easily done in stoichio-
metric reactions.
Figure 1. (η3-allyl)Pd complexes with a tethered sulfide ligand.
Scheme 1. Possible Products in a Pd-Catalyzed Allylic Alkylation
We want to employ the systems depicted in Figure 1 in
order to quantify the importance of the trans effect relative to
the steric bias inherent in a monosubstituted η3-allyl electro-
phile. To this end, we have isolated the complexes and
studied their reaction with a nucleophile. Further, the com-
plexes have been studied both in solid state and in solution to
confirm the proposed structures. We have also performed a
computational study of the complexes themselves as well as
their reactivity, to elucidate the source of the observed
selectivities in the allylic alkylation reaction.
It has long been recognized that ligands on Pd can influence
the regioselectivity of nucleophilic attack. In particular, the
large trans effect of phosphorus will enhance reactivity on the
allylic terminus trans to any phosphine.14 This phenomenon
was utilized in a breakthrough in asymmetric allylic alkylation
in the early 1990s, when three groups independently introduced
the phosphino-oxazoline class of ligands now known as
PHOX.15 Several other groups developed bidentate ligands
with two different coordinating heteroatoms,11 mostly phos-
phorus and nitrogen, but also, for example, sulfur.16
Quantifying the magnitude of the trans effect in the Tsuji-
Trost reaction and separating it from steric influences is not a
trivial task. A lower limit was demonstrated in a system where
the difference in trans effect between phosphines and chloride
gave regioretention up to 40%,17 but interpretation is compli-
cated by the many dynamic processes available to (η3-allyl)Pd
complexes, most of which are accelerated by the presence of
chloride.18 More recently, it was shown that, in the presence of a
simple P,N-ligand, the regioretention that would be expected
from the known difference in trans effect between P and N was
almost completely absent. This surprising result was attributed
to very efficient apparent rotation in the cationic (η3-allyl)Pd
intermediate.19 Thus, accurate measurement of the balance
between sterics and trans effects in the Tsuji-Trost reaction
requires negation of the apparent rotation. This can be achieved
by tethering one of the ligands to the allylic moiety. We
have performed preliminary computational and experimental
studies on systems with a tethered sulfide ligand (Figure 1).20
Experimental Results
Alkenes with tethered sulfide ligands, precursors to the com-
plexes in Figure 1, were synthesized from the corresponding
bromides (Scheme 2). Neutral (η3-allyl)Pd complexes 1 were
prepared by reaction of the alkenes with palladium trifluoro-
acetate and a base, followed by anion exchange with lithium
chloride. To prepare the cationic (η3-allyl)Pd complexes 2, the
neutral complexes were treated with triphenyl phosphine and
silver tetrafluoroborate, precipitating silver chloride. Com-
plexes with a dimethylene tether, 1a and 2a, were obtained in
moderate to high yield. Synthesis of complexes with a trimethy-
lene tether was more problematic and frequently yielded a
byproduct, 3 (X = Cl or PPh3), from an apparent hydride shift.
The preferred regioselectivity on nucleophilic attack for all
four complexes (1a,b and 2a,b) was tested in a standard alkyla-
tion reaction using sodium dimethyl malonate as nucleophile
1
(Scheme 3). Analyses by GC-MS and H NMR showed that
each complex gave rise to two products: the linear product, 4,
from the terminal attack, and the branched product, 5, from the
internal attack. The product distribution in each case is shown
in Table 1.
Looking first at the cationic phosphine complexes 2, we can
see that the regioselectivity is determined by the geometry of the
allylic moiety, not by the nature of the ligands. The selectivity
shifts from a preference for internal attack with the shorter
tether (2a) to a preference for terminal attack in the homologue
with an additional methylene unit (2b). Thus, it is clear that
the steric preference inherent in the allylic moiety is strong relative
to the influence from the trans effect difference. However, the
kinetic trans effect can be detected by an isodesmic comparison
of the chloride and phosphine complexes. When going from
˚
(14) Akermark, B.; Zetterberg, K.; Hansson, S.; Krakenberger, B.;
Vitagliano, A. J. Organomet. Chem. 1987, 335, 133–142.
(15) (a) von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32,
566–569. (b) Sprinz, J.; Helmchen, G. Tetrahedron Lett. 1993, 34, 1769–
1773. (c) Allen, J. V.; Coote, S. J.; Dawson, G. J.; Frost, C. G.; Martin, C. J.;
Williams, J. M. J. J. Chem. Soc., Perkin Trans. 1 1994, 2065–2072.
(16) (a) Pellissier, H. Chiral Sulfur Ligands: Asymmetric Catalysis;
RSC: Cambridge, 2009. (b) Evans, D. A.; Campos, K. R.; Tedrow, J. S.;
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Michael, F. E.; Gagne, M. R. J. Am. Chem. Soc. 2000, 122, 7905–7920.
(17) Svensen, N.; Fristrup, P.; Tanner, D.; Norrby, P.-O. Adv. Synth.
Catal. 2007, 349, 2631–2640.
(21) Itami, K.; Koike, T.; Yoshida, J.-I. J. Am. Chem. Soc. 2001, 123,
6957–6958.
(22) Krafft, M. E.; Sugiura, M.; Abboud, K. A. J. Am. Chem. Soc.
(18) Vrieze, K. In Dynamic Nuclear Magnetic Resonance Spectrosco-
py; Jackman, L. M., Cotton, F. A., Eds.; Academic Press: New York, 1975.
(19) Johansson, C.; Lloyd-Jones, G. C.; Norrby, P.-O. Tetrahedron:
Asymmetry 2010, 21, 1585–1592.
2001, 123, 9174–9175.
(23) (a) Krafft, M. E.; Fu, Z.; Procter, M. J.; Wilson, A. M.;
Hirosawa, C. Pure Appl. Chem. 1998, 70, 1083–1090. (b) Krafft, M. E.;
Wilson, A. M.; Fu, Z.; Procter, M. J.; Dasse, O. A. J. Org. Chem. 1998, 63,
1748–1749.
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(20) (a) Norrby, P.-O.; Akermark, B.; Hæffner, F.; Hansson, S.;
Blomberg, M. J. Am. Chem. Soc. 1993, 115, 4859. (b) Norrby, P.-O. Ph.
D. Thesis, KTH, Stockholm, 1992.

232 Organometallics, Vol. 30, No. 2, 2011
Kleimark et al.
Scheme 2. Synthetic Route to 1,2a and 1,2b
Scheme 3. Regioisomeric Products Formed in the Reaction with
Sodium Dimethyl Malonate
80:20). The selectivities now resemble the ones obtained with
isolated syn-alkyl complexes,7,25 as well as with the syn-compo-
nent in equilibrating syn-anti mixtures.8 We also note that the
results shown in Scheme 4 disprove the proposal of Krafft and
co-workers that the uncomplexed sulfide should be able to direct
the incoming nucleophile to the internal position.23
Several factors have been shown to influence the regioselectivity
of attack on unsymmetrically substituted (η3-allyl)Pd moieties. In
general, a monoalkyl substituent will shift the reactivity to the
terminal position, but the preference for internal attack can be
increased if the substituent is oriented in the anti-position.7,8 Thus,
the current results could be rationalized if the shorter tether induces
a preference for an anti-substituted η3-allyl. However, preliminary
results obtained with a specially designed molecular mechanics
force field20 indicate that the syn-configuration should be preferred
for both tethers, and in particular for the shorter one. Thus, an
explanation based on syn-anti equilibration seems unlikely. How-
ever, to be sure that the syn-configuration was preferred also in the
experimental study, the solid state of the complexes 1a,b and 2a,b
(Figure 1) were studied by X-ray diffraction, and the structures in
solution were studied by NMR spectroscopy.
Structure in Solution. All four complexes (1a,b and 2a,b) were
fully characterized by 1D- and 2D-1H NMR spectroscopy. The 1H
NMR spectra of the complexes were assigned by using COSY
experiments, and the structure was assigned by measuring the
coupling constants between the protons in the allylic moiety.
Primarily, the coupling constant between H2 and H3 is informative
for determining whether the complex is the syn- or the anti-isomer.
In the anti-isomer, where the H3 is in syn-position, the coupling
constant is in the range 6.5-8 Hz, and in the syn-isomer, where the
H3 is in anti-position, the coupling constant is in the range 11.5-
14 Hz.26 In all complexes, 1a,b and 2a,b, the coupling constant
between H2 and H3 was in the range 11-13 Hz, which confirmed
that all detectable complexes were syn-isomers in solution.
Table 1. Product Distribution from Reactions in Scheme 3
complex ligand X tether length linear 4 (%) branched 5 (%)
1a
1b
2a
2b
Cl
Cl
PPh3
PPh3
2
3
2
3
40
80
20
80
60
20
80
20
chloride to phosphine, the amount of branched product in-
creases when utilizing the smaller complexes, showing that
nucleophilic attack trans to phosphorus is more favorable than
attack trans to chloride, in agreement with known differences in
trans effect of these two ligands.24 We also note that the results
obtained by Krafft and co-workers in a catalytic system is the
same as what we see for the isolated complex 2a,23 indicating
that the tethered ligand is coordinated to Pd during the reaction.
Further, in their study they reported that using Pd(PPh3)4 gave
rise to mixed results, compared to the results when applying (η3-
allyl)PdPPh3Cl. The reason for this might be that the excess
PPh3 replaces the sulfide tether. To test this assumption, we
wanted to perform the reaction with a nucleophile under con-
ditions where the tethered sulfide does not coordinate to the
palladium. Since the dominant factor leading to coordination
of the sulfide is a chelate effect, it can be negated by utilization of
a stronger, chelate-assisted ligand, a phosphine. Since the com-
plex with the shorter tether seems to be under strain, it is even
possible that a sufficiently strong ligand can displace sulfur even
without chelate assistance. With this in mind, we reacted com-
plex 1a with two different competing ligands, either one equiva-
lent of dppe (1,2-(diphenylphosphino)ethane) or an excess of
PPh3, followed by treatment with the standard nucleophile, the
sodium salt of dimethyl malonate. The results, depicted in
Scheme 4, clearly show that both phosphine systems are able
to displace the tethered sulfide. In the absence of tethering and
differential trans influences, the selectivity becomes more simi-
lar to that of the system using the longer tether (Table 1, 1b;
Crystallographic Study. In the solid state all four complexes
feature palladium in a distorted square-planar coordination geom-
etry, with Pd surrounded by the sulfur atom and the allylic moiety
of the tethered ligand and either chloride or triphenylphosphine. In
1a and 1b the anionic chloride is coordinated to Pd, forming a
neutral complex, whereas in 2a and 2b the neutral phosphine ligand
makes the complexes cationic with noncoordinating BF4 as coun-
terion. In the crystal structure of 2a and 2b the BF4’s are disordered,
and this results in raised R values and thus poorer quality for the
overall structure determination especially for structure 1b. The
conformations of the two- and three-methylene-tethered complexes
(24) Coe, B. J.; Glenwright, S. J. Coord. Chem. Rev. 2000, 203, 5–80.
˚
(25) Sjogren, M.; Hansson, S.; Akermark, B.; Vitagliano, A. Orga-
˚
(26) Akermark, B.; Krakenberger, B.; Hansson, S.; Vitagliano, A.
€
nometallics 1994, 13, 1963–1971.
Organometallics 1987, 6, 620–628.

Article
Organometallics, Vol. 30, No. 2, 2011 233
Scheme 4. Selectivities with and without Coordination of the Tethered Sulfide Ligand
Table 2. Crystal and Refinement Data for 1a,b and 2a,b
[PdC11H13ClS]
[PdC12H15ClS]
[PdC29H28PS][BF4]
[PdC30H30PS][BF4]
1a
1b
2a
2b
formula
M
space group
PdC11H13ClS
319.12
Pcab
7.7780(14)
15.665(2)
19.090(3)
90
90
90
2326.0(6)
8
1.823
PdC12H15ClS
333.15
P21/c
9.250(2)
9.137(2)
15.844(4)
90
102.702(9)
90
1306.4(6)
4
1.694
PdC29H28BF4PS
632.75
P21/n
14.315(3)
9.8835(19)
20.117(4)
90
102.401(7)
90
2779.8(10)
4
1.512
PdC30H30BF4PS
646.78
Cc
14.005(4)
13.835(3)
15.730(5)
90
107.523(9)
90
2906.4(14)
4
1.478
˚
a/A
˚
b/A
˚
c/A
R/deg
β/deg
γ/deg
3
˚
V/A
Z
Dc/cm-3
μ(Mo KR)/mm-1
T/K
1.962
293(2)
1.751
293(2)
0.844
293(2)
0.809
293(2)
cryst size/mm
no. of rflns collected
no. of unique rflns (Rint
GOF on F2
0.25 ꢀ 0.25 ꢀ 0.20
0.25 ꢀ 0.25 ꢀ 0.20
0.30 ꢀ 0.20 ꢀ 0.05
0.20 ꢀ 0.20 ꢀ 0.10
14 306
2096 (0.0325)
1.062
8365
17 965
5083 (0.0642)
1.250
9518
4999 (0.0366)
1.076
)
2365 (0.0325)
1.137
0.0490/0.1072
final R1(F)a (I > 2σ(I)/wR2(F2)b
0.0358/0.0848
0.0379/0.0865
P
0.1020/0.1462
0.1214/0.1533
0.0442/0.0951
0.0532/0.0994
R1a/wR2(F2)b(all data)
0.0560/0.1111
P
P
P
a R1(F) = (||Fo| - |Fc||)/ |Fo|. b wR2(F2) = { [w(Fo2 - Fc2)2]/ [w(Fo2)2]}1/2
.
respectively are very similar, and all consist of syn-isomers in the
solid state. A summary of the crystal and refinement data can be
found in Table 2.
chains will adopt gauche geometries, which gives the result that the
sulfur phenyl orientations differ between the two tether geometries.
Sulfur is stereogenic in the complexes, and structure 2b has an
inverted sulfur stereochemistry compared to the other three com-
plexes. Again, the inversion at sulfur is a low-energy process, and the
preferred geometry is most probably determined by interactions with
the phosphine phenyl groups as well as with neighboring moieties in
the crystal. We note that, with the longer tether, the Pd-C3 bond
becomes slightly longer, and the syn substituent is closer to the plane
of the allyl moiety, indicating a less strained structure.
The crystal structure of 1a (Figure 2) is similar to the structure of
the previously reported chloro(syn-4,4-dimethyl-5-methylthiopent-
(1-3-η)enyl)palladium, 6.27 The phenyl substituent on sulfur in 1a
makes the Pd-S-C6 angle in 1a (119.6°) larger than the
Pd-S-Me angle in 6 (110.4°). The crystal structure of 2a mainly
differs from 1a in the rotation of the phenyl group on sulfur, a low-
energy distortion that will be determined primarily by nonbonded
interactions in the solid state.
In order to further elucidate the source of the anomalous
selectivity, we turned to a computational study, employing DFT
methods that have previously been shown to give good pre-
dictivity for Pd-assisted allylic alkylation.19,28
Computational Results
In our computational studies, the complete conformational
and configurational space of all structures were investigated
The structures with a three-carbon tether chain, 1b and 2b (Figure3),
are quite similar to their homologues 1a and 2a. The methylene
(28) (a) Butts, C. P.; Filali, E.; Lloyd-Jones, G. C.; Norrby, P.-O.;
Sale, D. A.; Schramm, Y. J. Am. Chem. Soc. 2009, 131, 9945–9957. (b)
Fristrup, P.; Ahlquist, M.; Tanner, D.; Norrby, P.-O. J. Phys. Chem. 2008,
112, 12862–12867.
(27) McCrindle, R.; Alyea, E. C.; Ferguson, G.; Dias, S. A.; McAlees,
A. J.; Parvez, M. J. Chem. Soc., Dalton Trans. 1980, 137–144.

234 Organometallics, Vol. 30, No. 2, 2011
Kleimark et al.
Figure 2. Molecular structure of 1a and 2a. Thermal ellipsoids enclose 50% probability. All hydrogen atoms and the disordered BF4
anion in 2a have been omitted for clarity.
Figure 3. Molecular structures of 1b and 2b. Thermal ellipsoids enclose 50% probability. All hydrogen atoms and the disordered BF4
anion in 2b have been omitted for clarity.
using a molecular mechanics force field specifically designed for
complexes like 120 and modified to fit the known structure of 6.27
All low-energy structures were reoptimized with DFT and used
as starting points for transition state searches, as outlined in the
Computational Methods section, vide infra.
all of the error originates from the Pd-S bond, which is too long
by approximately 0.1 A in the DFT structure. This is a system-
atic error that will occur in all our calculated structures. We can
therefore expect error cancellation when comparing related
structures.
Investigating the chloride complexes by molecular mechanics,
eight geometrical isomers of complex 1a and 12 of complex 1b
could be located, including both syn- and anti-isomers. All
isomers were reoptimized at the DFT level. The anti-isomers
were deemed unimportant due to their high energy, at least
˚
To validate the selected DFT method for (η3-allyl)palladium
complexes with a Pd-S bond, the ability to reproduce the
known X-ray structure 627 was tested. Overlaying all non-
hydrogen atoms of the X-ray and DFT-optimized structure
˚
gave a root-mean-square (rms) deviation of 0.0531 A. Almost

Article
Organometallics, Vol. 30, No. 2, 2011 235
Figure 4. Transition state for terminal attack on complex 2a.
Hydrogen atoms and most of the phenyl moieties were included
in the calculation but are hidden for clarity.
Figure 5. Length of the bonds observed in the X-ray structures
versus the regioselectivity in the nucleophilic attack.
Several factors influencing the regioselectivity have been
reported in the literature, as outlined in the Introduction. The
expected selectivity for nucleophilic attack on a syn-monosub-
stituted (η3-allyl)Pd is a strong preference for terminal attack,7,8
in reasonable agreement with the results for the long tether (2b),
but not for the short tether (2a). Increased preference for internal
attack is found for anti-isomers,7,8 but this possibility can be
excluded in the current case. Only the syn-complexes were
observed in both solid state and solution, and the computational
results also showed a large preference for the syn-isomers. Not
only were anti-isomers prohibitively high in energy, transition
state searches for such complexes also revealed that the barriers
to nucleophilic attack are high.
18 kJ/mol above the best syn-complex. For the syn-isomers of
the complexes, each tether length showed a strong preference for
one ring conformation, displaying the alternating gauche con-
formations generally found in chair cyclohexanes, as well as in
the previously reported X-ray structure of 6. For each complex
(1a and 1b), two low-energy conformations were selected for
further studies, differing only in the orientation of the sulfide
phenyl substituent. The resulting four structures were used as
starting points for optimization of the corresponding cationic
phosphine complexes (2a and 2b), for which no molecular
mechanics parameters were available. The optimized structures
were then employed in a transition state search with sodium
dimethyl malonate as the nucleophile. The coordination sphere
of the Na atom was solvated with two explicit ether molecules
(Me2O) to avoid nonphysical interactions with the substrate.
This small model, used together with standard continuum
solvation, has previously been used successfully to represent
THF coordination.28 For each approach vector of the nucleo-
phile, at least three rotameric forms were tested, but the discus-
sion below is based on the best (i.e., lowest energy) approaches
for each case. A typical transition state can be seen in Figure 4.
The preference for internal attack was calculated as the free
energy difference between the best nucleophilic attack on the
terminal and internal position, respectively. For reference, the
experimental values in Table 1 correspond to a ΔΔG‡exp = 4 kJ
mol-1 for 2a and -4 kJ mol-1 (a preference for terminal attack)
for 2b. The calculated results were found to depend strongly on
the actual method used. With a small basis set (method I), both
complexes prefer terminal attack; ΔΔG‡I = -2 kJ mol-1 for 2a
and -23 kJ mol-1 for 2b. Employing a larger basis set, method
Reactivities have also been quantified in terms of the
length of the breaking Pd-C bond, the preferred rotation
of the η3-allyl moiety, and steric hindrance.13 In particular, it
was found that a longer Pd-C bond corresponds to a more
˚
reactive allyl terminus, with each 0.01 A elongation giving
approximately a doubling in reactivity.13 We therefore com-
pared the reactivity in the alkylation reaction of the allylic
positions in the complexes with the observed bond length in
the solid state structures (Figure 5). The calculated structures
(in the Supporting Information) showed similar trends.
We can immediately see that the bond lengths detected in
the solid state do not give the expected correlation with
reactivity. In complex 1a, the preferred nucleophilic attack
occurs on the allylic carbon atom with the shortest Pd-C
bond. In complex 2a the preferred nucleophilic attack was
observed at the internal carbon atom, which is the allylic
carbon atom with the longest Pd-C bond. Another observa-
tion of preferred nucleophilic attack on an allylic carbon
with the longest Pd-C bond was in complex 1b, where a
terminal attack was preferred. In complex 2b, where the
longest bond was trans to the donor atom with the expected
stronger trans influence (P), the preferred nucleophilic attack
was at the other, terminal, carbon atom. In an isodesmic
comparison, we can see a modest trans influence, in that
bonds trans to P are slightly longer than the corresponding
bonds trans to Cl. Thus, Pd-C3 in 2a is longer than Pd-C3
in 1a, and the same is true for 2b versus 1b. With the shorter
tether, there is also a slight increase in the reactivity of the
bond trans to P. However, in 2b the kinetic trans effect is
completely absent, in that no change is observed when going
from a chloride to phosphine auxiliary ligand, even though
there is a significant trans influence.
II, yielded a substantially better result for 2a, ΔΔG‡ = 5 kJ
II
mol-1, in good agreement with the experimental results. For 2b,
the results are still in qualitative agreement with the experi-
mental results, but the absolute preference for terminal attack is
strongly exaggerated, 31 kJ mol-1. Interestingly enough, apply-
ing a vdW correction (method III) brings the energy difference
much closer to the experimental values: ΔΔG‡III = 6 kJ mol-1
for 2a and -10 kJ mol-1 for 2b. It should be noticed that
independent of the method, the trend is correct in that the
amount of internal attack decreases when going from short to
long tether.
Discussion
The computational studies have been able to reproduce the
experimental selectivities with a fair accuracy. However, this
does not in itself tell us why the reactivity shifts as a function
of the tether length. In order to shed light on the situation, we
therefore subjected the structures of 2a and 2b, and the
transition states resulting from them, to further scrutiny.
The calculated bond lengths are similar to those observed
in the X-ray structures (Table 3). The Pd-C3 bond in the

236 Organometallics, Vol. 30, No. 2, 2011
Kleimark et al.
Figure 6. Different orientations of the η3-allyl with respect to
the S-Pd-P(Cl) plane.
˚
Table 3. Selected Bond Lengths (A) in the Allylic Moiety for 1a,b
and 2a,b in the X-ray and Two Lowest Energy DFT Structures for
Each Complex
structure
Pd-C1
Pd-C3
1a (X-ray)
2.175(4)
2.174
2.169
2.174(8)
2.163
2.166
2.151(10)
2.220
2.215
2.194(7)
2.186
2.186
2.116(3)
2.155
2.156
2.145(6)
2.193
2.202
2.185(9)
2.217
2.216
2.232(7)
2.290
2.300
1a (DFT_1)
1a (DFT_2)
1b (X-ray)
1b (DFT_1)
1b (DFT_2)
2a (X-ray)
2a (DFT_1)
2a (DFT_2)
2b (X-ray)
2b (DFT_1)
2b (DFT_2)
Figure 7. Overlay of two low-energy conformers each of 2a
(gray) and 2b (black), showing steric interactions with a nucleo-
phile attacking the internal position. Phenyl hydrogens are
hidden for clarity.
Table 4. Torsion Angles (deg) of the Allylic Moiety for 1a,b and
2a,b in the X-ray and Two Lowest Energy DFT Structures for
each Complex
C1 to plane
[P(or Cl)-Pd-S]a
C3 to plane
[P(or Cl)-Pd-S]a
structure
larger tether, 2b, is to some extent elongated in the calculated
structure, but previous results have shown that similar
complexes can give anomalies in the bond trans to phos-
phorus.29 Overall, the agreement between the DFT struc-
tures and the crystallographic data is good (Table 3).
It has also been shown that reactivity can be correlated
with the enforced product-like rotation of the (η3-allyl)Pd
moiety in the ground state.13,30 We have measured this
rotation as displacements of the two terminal carbons in
the η3-allyl from the S-Pd-P(or Cl) plane (Figure 6).
Figure 6 shows different ways the η3-allyl can orient itself
with respect to the S-Pd-P(Cl) plane. The symmetric fashion,
represented by situation B in Figure 6, will not induce any
product preference. In the other two orientations, A and C, there
will be a preferred pathway to form product due to the prerota-
tion of the η3-allyl toward one of the two isomeric products.30 In
situation A, the internal attack of the nucleophile (trans to P)
will be favored, since this orientation of the allylic moiety
resembles the coordinated product formed from this attack
(structure D in Figure 6). Likewise, situation C resembles the
product formed from a terminal attack (trans to S, structure E in
Figure 6). In both X-ray and calculated structures (Table 4), the
shorter tether has an orientation that resembles situation A and
therefore should give a preference for the internal attack. This
correlates satisfactorily to the experimental results. In the case of
the longer tether, it has a more symmetric orientation (situation
B), and it is therefore harder to rationalize the product forma-
tion based on the enforced rotation of the allyl.
1a (X-ray)
0.309
0.144
0.087
-0.107
-0.067
-0.294
0.072
0.098
0.106
-0.116
-0.055
-0.328
-0.199
-0.311
-0.121
-0.419
-0.330
-0.275
-0.317
-0.268
-0.162
-0.185
-0.078
-0.607
1a (DFT_1)
1a (DFT_2)
1b (X-ray)
1b (DFT_1)
1b (DFT_2)
2a (X-ray)
2a (DFT_1)
2a (DFT_2)
2b (X-ray)
2b (DFT_1)
2b (DFT_2)
a Positive value if situated on the same side of the plane as H2.
Steric factors have been shown to have a strong influence
on the relative reactivity of the two termini of the η3-allyl. The
selectivity in nucleophilic attack has been shown to correlate well
with the energy cost of adding a steric probe at a distance of
2.5 A from the reactive terminus,13 close to the position of the
˚
nucleophile determined in the current study. A strong indication
that vdW interactions could be a determining factor in the
current case comes from the observation that it was necessary
to apply a vdW correction31 to the B3LYP calculations to get
more than a qualitative agreement with the experimental results
for 2b, whereas no significant influence was seen for 2a. When
overlaying the lowest energy conformers of the two structures
(Figure 7), it is clear that there is a significant difference in
the interaction with the incoming nucleophile by the methylene
group adjacent to the allylic moiety. The orientation of the
tethered substituent in 2b is similar to the orientation of
the substituent found in unstrained syn-complexes,30 as expected
from the observed selectivity. The tether in 2a is bent away from
the incoming nucleophile, substantially decreasing the steric
hindrance at this position, in good agreement with the experi-
mental results.
˚
(29) Hagelin, H.; Akermark, B.; Norrby, P.-O. Organometallics 1999,
18, 2884–2895.
(30) (a) Frost, C. G.; Howarth, J.; Williams, J. M. J. Tetrahedron:
Asymmetry 1992, 3, 1089–1122. (b) Reiser, O. Angew. Chem., Int. Ed.
~
€
Engl. 1993, 32, 547–549. (c) Pena-Cabrera, E.; Norrby, P.-O.; Sjogren, M.;
Vitagliano, A.; deFelice, V.; Oslob, J.; Ishii, S.; Åkermark, B.; Helquist, P. J.
Am. Chem. Soc. 1996, 118, 4299–4313. (d) Dierkes, P.; Ramdeehul, S.;
Barloy, L.; De Cian, A.; Fischer, J.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.;
Osborn, J. A. Angew. Chem., Int. Ed. 1998, 37, 3116–3118.
(31) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys.
2010, 132, 154104.

Article
Organometallics, Vol. 30, No. 2, 2011 237
Table 5. Average Length of the Forming C-C Bond in Nucleo-
philic Attack on 2
and subjected to vibrational analysis to validate the nature of the
stationary points as ground or transition states, respectively.
Vibrational contributions to the free energy were calculated at
373.15 K. Solution phase energies were obtained by single-point
calculations on the gas phase structure. Solvent was modeled by
Jaguar’s Poisson-Boltzmann method38 with parameters de-
internal attack
˚
distance (A)
terminal attack
˚
distance (A)
complex
2a
2b
2.31
2.23
2.29
2.26
˚
scribing dichloromethane (ε = 9.08, probe radius 2.33237 A);
the results are virtually identical with parameters for THF.28
The solution phase Gibbs free energy was estimated by adding
the gas phase vibrational contribution to the single-point solu-
tion phase energy (method I). Effects of a large basis set were
estimated by replacing the potential energies by single-point
energies obtained using a larger basis set, LACVP**þþ
(method II). Starting from method II, the nonbonded interac-
tions were corrected using the approach of Grimme31 as a single-
point correction (method III).
Analysis of the forming bond lengths in the transition
states for attack on 2a and 2b confirms the importance of steric
repulsion in determining selectivity. In accordance with the
general Bell-Evans-Polanyi theory,32 and also with the more
specific Hammond postulate,33 increased steric hindrance
should result in a “later” transition state, that is, a shorter
forming bond.34 The bond lengths shown in Table 5 confirm
that the “earliest” attack is for the internal position in 2a, with a
0.02 A shorter forming bond for the terminal position in the
same complex. The opposite trend is seen in 2b, where the
˚
forming bond at the internal position is 0.03 A shorter than the
one at the terminal position, indicating significant steric hin-
drance at the internal position of 2b, but not 2a.
In the transition state searches the sodium ion was chelated to
both carbonyl oxygens of the nucleophilic enolate, forming a
relatively rigid six-membered ring (Figure 4). To avoid a non-
physical electrostatic collapse in the gas phase calculations, the
coordination sphere of sodium was filled with two small solvent
models, Me2O. Initial transition state structures were located by
˚
˚
driving the forming C-C bond with 0.1 A increments and
optimizing all other degrees of freedom. All transition states
were refined by eigenmode following and verified by the pre-
sence of exactly one imaginary frequency. Visual inspection
confirmed that the eigenvector corresponded well to the forma-
tion of the new C-C bond.
Conclusions
Experimental studies of (η3-allyl)Pd complexes with teth-
ered ligands indicate that the geometry of the allyl moiety is
more important than electronic effects in determining selec-
tivity of nucleophilic attack. However, a weak trans effect on
the product selectivity could be observed by varying the
nature of the auxiliary ligand.
A computational investigation could reproduce the trend
in selectivities using standard DFT methods, but a reason-
able quantitative agreement was obtained only when a vdW
correction was applied, in agreement with recent studies of
organometallic reactivity.35
Several previously suggested factors for controlling regio-
selectivity in nucleophilic attack on (η3-allyl)Pd systems were
evaluated in order to rationalize the observed selectivities.
These include observable geometric factors such as the
length of the Pd-C bond and the ground state rotation of
the allyl moiety, as well as interactions with the nucleophile
and trans effects from the ligands on Pd. In the current case, a
combination of the rotation of the allylic moiety and an
important steric repulsion appear to be the dominant factors
in determining regioselectivity.
Experimental Section
General Procedures. Products were identified by NMR spec-
troscopy and GC-MS. H NMR spectra were recorded on a
1
JEOL Eclipse 400 instrument, operating at 400 MHz for the
recording of 1H. Samples were dissolved in CDCl3, and chemical
shifts are given in ppm relative to residual CHCl3 (7.27 ppm).
GC-MS were run on a Varian 3400 GC with a Varian Saturn
2000 MS, with SB-5 MS columns; helium gas was used as carrier
gas. GC were run on a Varian 3900, with CP-SIL 8 CB columns;
hydrogen gas was used as carrier gas.
Elemental analyses were performed by Analytische Labora-
torien, Gummersbach, Germany.
X-ray diffraction: crystals were mounted on glass needles and
transferred to a Rigaku R-AXIS IIc image plate system. Dif-
fracted intensities were measured at 293(2) K, using graphite-
˚
monochromated Mo KR radiation (λ = 0.71073 A) from a
Rigaku RU-H3R rotating anode operating at 50 kV and 50 mA.
A total of 90 oscillation photos with a rotation angle of 2° were
collected. An empirical absorption correction was applied using
the REQAB program. The structures were solved using the
program SIR-9239 and refined using SHELX-97,40 operating in
the WinGX program suite.41 All non-hydrogen atoms were
refined anisotropically, and the allylic hydrogen atoms were
refined where the data quality so allowed and otherwise included
in calculated positions and refined using a riding model. Struc-
tures were drawn using ORTEP341 for Windows.
Computational Methods
The different conformations of complexes 1a and 1b were
generated using a modified MM2 force field20 and used as
starting points for further calculations. All structures have been
optimized in Jaguar, with the B3LYP hybrid functional36 and
the LACVP* basis set.37 The complexes were optimized in vacuo
All reactions were performed under a nitrogen atmosphere in
oven-dried glassware. THF was distilled from Na/benzophe-
none, and CH2Cl2 and pyridine were distilled from CaH2, all
under a nitrogen atmosphere. Commercially available reagents
(32) (a) Bell, R. P. Proc. R. Soc. London, Ser. A 1936, 154, 414–429. (b)
Evans, M. G.; Polanyi, M. J. Chem. Soc., Faraday Trans. 1936, 32, 1333–
1360. (c) For a discussion see: Jensen, F. Introduction to Computational
Chemistry; Wiley: Chichester, 1999.
(33) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334–338.
(34) Norrby, P.-O. J. Mol. Struct. (THEOCHEM) 2000, 506, 9–16.
(35) Averkiev, B. B.; Zhao, Y.; Truhlar, D. G. J. Mol. Catal. A 2010,
324, 80–88.
(36) (a) Becke, A. D. Phys. Rev. A 1988, 38, 3098–3100. (b) Lee, C. T.;
Yang, W. T.; Parr, R. G. Phys. Rev. B 1988, 37, 785–789. (c) Stephens, P. J.;
Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994, 98,
11623–11627.
(38) (a) Tannor, D. J; Marten, B.; Murphy, R.; Friesner, R. A.;
Sitkoff, D.; Nicholls, A.; Ringnalda, M.; Goddard, W. A., III; Honig, B.
J. Am. Chem. Soc. 1994, 116, 11875–11882. (b) Marten, B.; Kim, K.; Cortis,
C.; Friesner, R. A.; Murphy, R. B.; Ringnalda, M. N.; Sitkoff, D.; Honig, B.
J. Phys. Chem. 1996, 100, 11775–11788.
(39) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Gualardi, A.
J. Appl. Crystallogr. 1993, 26, 343–350.
(37) LACVP basis sets use 6-31G for main group elements, and the
Hay-Wadt ECP for Pd: Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82,
299–310.
(40) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112–122.
(41) (a) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837–838.
(b) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.

238 Organometallics, Vol. 30, No. 2, 2011
Kleimark et al.
were used as delivered unless stated otherwise. TLC was per-
formed using alumina plates coated with silica gel 60, F254. The
plates were visualized by using a mixture of 2% KMnO4 and 4%
K2CO3(aq) followed by warming with a heat gun, which resulted
in yellow spots. Column chromatography was performed using
silica gel 60, 0.04-0.06 mm.
6-(Phenylthio)hex-1-ene. Thiophenol (2.0 mL, 15 mmol) was
added to a degassed solution of NaOH (0.9 g, 22.5 mmol, in
3 mL of H2O), under a N2 atmosphere. The solution was stirred
for 30 min, until it had reached room temperature. Thereafter
6-bromo-1-hexene (1.34 mL, 10 mmol) was added droppwise.
The reaction mixture was stirred at room temperature under N2
for 16 h. The product was extracted with Et2O (3 ꢀ 15 mL) and
then washed with H2O (15 mL) and brine (15 mL) and dried with
Na2SO4. After evaporation of the solvent, the crude product was
collected as a light yellow oil (1.89 g, 9.8 mmol, 98%). 1H NMR
(400 MHz, CDCl3): δ (ppm) 7.24-7.25 (m, 4H), 7.13-7.20 (m,
1H), 5.0 (dm, 1H), 4.95 (dm, 1H), 2.92 (t, 2H), 2.07 (app. q, 2H),
1.67 (app. p 2H), 1.53 (app. p 2H).
evacuated and refilled with N2 two times and then stirred for 1 h.
The formed precipitate was filtered off through a Pasteur pipet
with Celite, and after evaporation of the solvent the product was
collected as a bright yellow crystalline foam (367 mg, 0.58 mmol,
97%). A small sample was recrystallized from CH2Cl2/Et2O,
1
which gave the product as light yellow needles. H NMR (400
MHz, CDCl3): δ (ppm) 7.32-7.44 (m, 10H), 7.23-7.31 (m, 8H),
7.16-7.22 (m, 2H), 6.20-6.30 (app. sextet, 1H), 5.74-5.84 (m,
1H), 4.24-4.33 (app. dt, 1H), 4.05 (app. d, 1H), 4.00 (dd, 1H),
3.57 (app. d, 1H), 2.47- 2.58 (m, 1H), 2.32-2-45 (m, 1H). Anal.
Calcd for C29H28BF4PPdS: C, 55.04; H, 4.46. Found: C, 54.91;
H, 4.60.
(syn-6-Phenylthiohex(1-3-η)enyl)(triphenylphosphine)palla-
dium Tetrafluoroborate (2b). As 2a, but starting from 1b (57 mg,
0.17 mmol), yielding the product as a light yellow foam (108 mg,
0.167 mmol, 98%). A small sample was recrystallized from CH2Cl2/
Et2O, which gave the product as light yellow needles. 1H NMR (400
MHz, CDCl3): δ (ppm) 7.17-7.43 (m, 20H), 5.78 (dt, 1H), 5.48 (m,
1H), 4.18 (br d, 1H), 3.30 (br d, 1H), 2.92 (m, 1H), 2.69.2.82 (m,
1H), 2.47 (br d, 1H), 2.25-2.35 (m, 1H), 2.12 (br q, 1H), 1.72 (br q,
1H). Anal. Calcd for C30H30BF4PPdS: C, 55.71; H, 4.68. Found: C,
55.58; H, 4.66.
5-(Phenylthio)pent-1-ene. As previous (1.68 g, 9.5 mmol,
1
95%). H NMR (400 MHz, CDCl3): δ (ppm) 7.24-7.34 (m,
4H), 7.13-7.20 (m, 1H), 5.72-5.84 (m, 1H), 5.04 (dm, 1H), 4.98
(dm, 1H), 2.92 (br t, 2H), 2.19 (app. br q, 2H), 1.74 (app. p, 2H).
Chloro(syn-5-phenylthiopent(1-3-η)enyl)palladium (1a). 5-(Phe-
nylthio)pent-1-ene (178 mg, 1.0 mmol) was dissolved in THF (2 mL,
dry), and Pd(OCOCF3)2 (332 mg, 1.0 mmol) was added together
with 2 mL of dry THF, and the deep red solution was stirred for
30 min, under N2. DIPEA (175 μL, 1.0 mmol) was added dropwise,
and LiCl (47 mg, 1.1 mmol) was added after 5 min. The black
solution was stirred for 20 min; then the solvent was evaporated and
the black residue was redissolved in CH2Cl2 and filtered through a
Pasteur pipet with Celite. The crude product was purified by flash
chromatography (CH2Cl2/MeOH, 20:1) and thereafter recrystal-
lized from CH2Cl2/Et2O, yielding the product as light yellow needles
General Procedure for the Allylic Alkylation. NaH (6 mg, 0.15
mmol, 60% suspension in oil) was suspended in dry THF
(1 mL), and the flask was evacuated and refilled with N2.
Dimethyl malonate (0.15 mmol, 17 μL) was added dropwise to
the suspension, which turned clear after the addition. The
solution was stirred at room temperature for 10 min.
The malonate solution was added to the palladium complex
(0.1 mmol) in dry CH2Cl2 (1 mL) under a N2 atmosphere. The
reaction mixture was stirred for 3 h, then diluted with Et2O
(5mL) andwashedwithHCl(1M, 3mL), H2O (5 mL), and brine (5
mL). The organic solution was dried over Na2SO4 and filtrated
through Celite, and the crude product mixture was analyzed by GC-
MS and 1HNMR. For further analysis the products (4a,b and 5a,
except 5b due to low yield) were purified by column chromatogra-
phy using EtOAc/pentane (1:5). The analyses were in agreement
with the previously reported structures.23
1
(0.140 mg, 0.44 mmol, 44%). H NMR (400 MHz, CDCl3): δ
(ppm) 7.77-7.82 (m, 2H), 7.32-7.44 (m, 3H), 5.72-5.81 (m, 1H),
4.30 (dt, 1H), 4.16 (dd, 1H), 3.86 (ddd, 1H), 3.64 (dt, 1H), 3.15 (app.
d, 1H), 1.99-2.15 (m, 2H). Anal. Calcd for C11H13ClPdS: C, 41.40;
H, 4.11. Found: C, 41.23; H, 3.99.
Dimethyl 2-(5-(Phenylthio)pent-2-en-1yl)malonate (4a). 1H
NMR (400 MHz, CDCl3): δ (ppm) 7.24-7.34 (m, 4H),7.15-
7.20 (m, 1H), 5.52-5.62 (m,1H), 5.39-5.48 (m, 1H), 3.74 (s,
6H), 3.42 (t, 1H), 2.91 (t, 2H), 2.60 (app. t, 2H), 2.31 (app. q,
2H).
Chloro(syn-6-phenylthiohex(1-3-η)enyl)palladium (1b). 6-(Phe-
nylthio)hex-1-ene (1.0 mmol, 192 mg) was dissolved in dry THF
(3 mL), and Pd(OCOCF3)2 (1.0 mmol, 332 mg) was added together
with 2 mL of dry THF. Directly after, NaHCO3 (252 mg, 3 mmol)
was added, under N2. The solution went from deep red to almost
black. The reaction was stirred for 16 h. LiCl (63.6 mg, 1.5 mmol)
was added, and after 20 min the solvent was evaporated and the
black residue was redissolved in CH2Cl2 and filtered through a
Pasteur pipet with Celite. The crude product was purified by flash
chromatography (CH2Cl2/MeOH, 20:1), yielding the product as a
crystalline foam (0.096 mg, 0.29 mmol, 29%). A small sample was
recrystallized from CH2Cl2/Et2O, which gave the product as orange
crystals. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.80-7.85 (m, 2H),
7.36-7.42 (m, 3H), 5.17-5.28 (m, 1H), 4.42 (dd, 1H), 3.45 (dt, 1H),
3.36 (app. d, 1H), 3.16 (app. ddd, 1H), 2.25-2.41 (m, 2H), 2.27 (dt,
1H), 1.61-1.74 (app. q, 1H), 1.45-1.57 (br q, 1H). Anal. Calcd for
C12H15ClPdS: C, 43.26; H, 4.54. Found: C, 43.18; H, 4.41.
Dimethyl 2-(6-(Phenylthio)pent-2-en-1yl)malonate (4b). 1H
NMR (400 MHz, CDCl3): δ (ppm) 7.24-7.34 (m, 4H),
7.13-7.20 (m, 1H), 5.35-5.56 (m, 2H), 3,72 (s, 6H), 3.41 (t,
1H), 2.88 (t, 2H), 2.58 (app. t, 2H), 2.12 (app. q, 2H), 1.67
(app. p, 2H).
Dimethyl 2-(5-(phenylthio)pent-1-en-3yl)malonate (5a). 1H
NMR (400 MHz, CDCl3): δ (ppm) 7.24-7.34 (m, 4H),
7.13-7.20 (m, 1H), 5.58-5.69 (m, 1H), 5.12-5.19 (m, 2H),
3.67 (s, 3H), 3.67 (s, 3H), 3.39 (d, 1H), 2.91-3.02 (m, 2H),
2.75-2.84 (m, 1H), 1.73-1.83 (m, 1H), 1.59-1.71 (m, 1H).
Acknowledgment. The Swedish Research Council is
gratefully acknowledged for support. We want to thank
Professors Paul Helquist and Aldo Vitagliano for valu-
able input in the early phase of the project.
(syn-5-Phenylthiopent(1-3-η)-enyl)(triphenylphosphine)palla-
dium Tetrafluoroborate (2a). The chloro complex 1a (191 mg,
0.6 mmol) was dissolved in dry CH2Cl2 (4 mL) under a N2
atmosphere and added to PPh3 in dry CH2Cl2 (1 mL). After
5 min, AgBF4 (126.5 mg, 0.65 mmol) was added to the solution
and rinsed down with dry CH2Cl2 (2 mL). The solution was
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